Lookup NU author(s): Dr Peter Gallagher,
Dr Stuart Watson,
Professor Nicol Ferrier,
Professor Allan Young
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Background: It has been suggested that hypercortisolemia may cause or exacerbate both neurocognitive impairment and symptoms in schizophrenia. We hypothesized that antiglucocorticoid treatments, particularly glucocorticoid receptor (GR) antagonists, would improve neurocognitive functioning and clinical symptoms in this disorder. Method: Twenty patients with schizophrenia were treated with 600 mg/day of the GR-antagonist mifepristone (RU-486) or placebo for 1 week in a double-blind, crossover design. Neurocognitive function was evaluated at baseline and 2 weeks after each treatment. Neuroendocrine profiling was preformed at these times and also immediately after each treatment. Symptoms were evaluated weekly. Results: Mifepristone administration resulted in a temporary two- to threefold increase in plasma cortisol levels (p < .0001). No sigtnificant effects were observed on any measure of neurocognitive function, including the primary outcome measures of spatial working memory and declarative memory. Minor changes in symptoms occurred in both arms of the study and were indicative of a general improvement over time, irrespective of treatment. Conclusions: In contrast to our earlier report of positive effects in bipolar disorder, these data suggest that the GR-antagonist mifepristone has no effect on neurocognitive function or symptoms in this group of patients with schizophrenia. Future studies in schizophrenia should examine patients with demonstrable hypothalmic-pituitary-adrenal axis dysfunction.
Author(s): Gallagher P, Watson S, Smith MS, Ferrier IN, Young AH
Publication type: Article
Publication status: Published
Journal: Biological Psychiatry
ISSN (print): 0006-3223
ISSN (electronic): 1873-2402
Publisher: Elsevier Inc.
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